Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation

BackgroundHepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents.ObjectivesTo define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT.MethodsIn this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis.ResultsA total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2–25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2–40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96).ConclusionOur study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.     

Total pancreatectomy with islet autotransplantation: an overview

Pain control is one of the most challenging aspects in the management of chronic pancreatitis. Total pancreatectomy can successfully relieve the intractable abdominal pain in these patients but will inevitably result in insulin-dependent diabetes. Islet autotransplantation aims to preserve, as far as possible, the insulin secretory function of the islet cell mass thereby reducing (or even removing) the requirement for exogenous insulin administration after a total pancreactomy. Despite the relatively small number of centres able to perform these procedures, there are important technical variations in the details of their approaches. The aim of this review is to provide details of the current surgical practice for total pancreatectomy combined with islet autotransplantation, and outline the potential advantages and disadvantages of the variations adopted in each centre.     

生长激素、肝细胞生长因子和烟酰胺对人胎胰岛细胞的增殖作用

目的研究生长激素(GH)，肝细胞生长因子(HGF)和烟酰胺(NIC)对体外培养的人胎胰岛细胞的增殖作用及其交互作用。方法采用La(2^7)正交设计法在体外培养的人胎胰岛细胞的各组中分别加入不同浓度及组合的GH，HGF和NIC，培养48h后，收集各孔细胞，DTZ染色，计数。结果GH，HGF和NIC均起主要作用，HGF和NIC的交互作用不可忽视，最佳的生长因子组合及适配浓度为GH(100ng／ml)HGF(25ng／ml)NIC(100mmol／L)。结论GH，HGF和NIC均能促进体外培养的胰岛细胞的增殖，且组合GH(100ng／ml)HGF(25ng／ml)NIC(100mmol／L)的作用最大。     

糖尿病脑内胰岛移植临床初步研究(附三例报告)

本文报告胰岛细胞脑内移植治疗I型糖尿病共3例,分别经过3个月、4个月、6个月的临床观察,其临床症状明显改善或消失,空腹血糖由移植前平均12.38mmol/L下降至7.77mmol/L;3例患者普通胰岛素用量平均每日62.3~u,移植后第21～30天均完全停用胰岛素,其中1例已持续撤离胰岛素治疗达5个月。观察结果提示:胰岛移植物在患者的脑内成活,并具有良好的内分泌功能。     

Culture Medium Modulates Proinflammatory Conditions of Human Pancreatic Islets Before Transplantation

A portion of transplanted islets is lost during engraftment as a result of stressful events, involving hypoxia and production of proinflammatory molecules by islets. Two of these molecules (monocyte chemoattractant protein-1, CCL2/MCP-1 and tissue factor, TF) are directly correlated with reduced graft function. We evaluated which factors reduce islet proinflammatory conditions. In particular the effects of different culture media supplemented with proteins or antioxidant agents on CCL2/MCP-1 and TF human islet release were evaluated. We observed that human islets after culture in final wash culture medium (FW) significantly decreased CCL2/MCP-1 release and TF production compared with CMRL and M199. These effects were independent from the type of protein added to the media (human serum, human albumin, fetal calf serum). Glutathione in FW further decreased CCL2/MCP-1 in a dose-dependent manner. Culture conditions can modulate the proinflammatory state of islets, and could be used in clinical islet transplantation to reduce inflammation during engraftment.     

Surgical management of endocrine tumor of the pancreas in Japan

Endocrine tumor of the pancreas is potentially malignant. A multicenter analysis of these tumors was conducted to clarity the present status of their surgical management and the subsequent long-term surgical results. The Japan pancreatoduodenectomy (JPD) study group carried out the study; 368 patients were enrolled and variables related to tumor characteristics, surgery, and survival were retrospectively analyzed. There were 222 patients with functioning tumor and 143 patients with nonfunctioning tumor. Malignant tumor was found in 140 of 368 (38%) of the patients, and 63/140 (45%) of these patients had metastatic lesion; the most common site of the metastasis was liver 34/136 (25%), followed by regional lymph nodes 26/136 (19%). Pancreatic resection was performed in 91% of patients with nonfunctional tumor and in 83% of those with malignant tumor, and 73% of the pancreatic resections were done with lymph node dissection. The overall 5-year actuarial survival rate was 76% in patients with malignant tumor. The actuarial 5-year survival rate was 93% in the patients without metastasis and 83% in patients who received curative resection. Multivariate analysis showed that the presence or absence of synchronous metastasis was the sole significant prognostic factor. The results suggest that: (i) malignant endocrine tumor of the pancreas is a curable malignancy when pancreatic resection with lymph node dissection is adopted and (ii) that synchronous metastasis is the dominant prognostic factor. This study was carried out as a group project. The authors' institutions are as follows     

大鼠胎胰胰岛组织培养及移植的实验观察

本实验对培养中的大鼠胎胰胰岛组织及其移植后的形态功能进行了观察。结果表明,大鼠胎胰经短期培养,不仅内分泌胰岛β细胞的活力保存良好,而且胰外分泌腺泡大大减少以致消失。21只糖尿病大鼠,同种移植经过7天培养的胎胰胰岛,未用免疫抑制剂,术后糖尿病缓解率76.2％。     

烟酰胺对高糖介导胰岛细胞bax及bcl-2表达的影响

目的 探讨烟酰胺对高糖环境下胰岛细胞bax及bel-2蛋白表达的影响。方法 体外培养大鼠胰岛细胞，应用免疫组化方法检测培养液中葡萄糖终浓度为22．2mmol／L及加入烟酰胺后胰岛细胞bax及bcl-2蛋白表达。结果 培养液中葡萄糖终浓度为22．2mmol／L时，胰岛细胞bax表达阳性，bcl-2表达较对照组降低。加入烟酰胺后bax表达降低，bcl-2表达增强。结论 烟酰胺能够上调bcl-2表达，下调bax表达，在高糖介导的胰岛细胞损伤中起一定作用。     

大鼠实验性脾虚证胰岛A、B和D细胞的免疫组织化学研究

用免疫组织化学ＰＡＰ法显示实验性脾虚组和正常对照组大鼠胰岛Ｂ细胞（胰岛素细胞）、Ａ细胞（胰高血糖素细胞）和Ｄ细胞（生长抑素细胞）．结果显示，实验组胰岛素分泌升高（Ｐ＜０．０１），胰高血糖素和生长抑素分泌下降（Ｐ＜０．０５）。实验结果提示大鼠胰岛Ａ、Ｂ和Ｄ细胞分泌活动的变化与脾虚证的症候可能有密切关系。     

川芎嗪对环孢素引起的大鼠胰岛β细胞毒性防护作用的实验研究

给大鼠应用环孢素(CsA)50mg/kg·d灌胃,共10天,引起高血糖症及血浆和胰腺组织中胰岛素水平下降。同时联合应用川芎嗪(LIG)50mg/kg·d共10天,能有效地防止和(或)减轻CsA引起的上述变化。LIG还有效地减轻了CsA引起的尿血栓素B_2和尿血栓素B_2/6-酮-前列腺素F_(1α)值的升高。结果提示LIG对CsA引起的胰岛β细胞毒性的防护作用可能与调节前列胰素代谢有关。